aryl hydrocarbon receptor repressor (AhR repressor, AhRR, AHRR, KIAA1234)
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Function
- mediates dioxin toxicity
- involved in regulation of cell growth & differentiation
- represses the transcription activity of AHR by competing with this transcription factor for heterodimer formation with the ARNT & subsequently binding to the xenobiotic response element (XRE) sequence present in the promoter regulatory region of variety of genes
- represses CYP1A1 by binding the XRE sequence & recruiting ANKRA2, HDAC4 &/or HDAC5
- autoregulates its expression by associating with its own XRE site
- interacts with ARNT, ANKRA2, HDAC4 & HDAC5
Structure
- contains 1 basic helix-loop-helix (bHLH) domain
- contains 1 PAS (PER-ARNT-SIM) domain
Compartment
- cytoplasm, nucleus
- predominantly in nuclear compartment
- first cytoplasmic, translocates into nucleus upon interaction with ARNT cytoplasm
Alternative splicing
named isoforms=3
Expression
- highly expressed in testis, lung, ovary, spleen & pancreas
- highly expressed in mononuclear cells (MNCs) from umbilical cord blood
- isoform 3 is highly expressed in lung, kidney, spleen & thymus
- down-regulated malignant tissue from different anatomical origins, including colon, breast, lung, stomach, cervix, & ovary
- induced by 3-methylcholanthrene (3-MC) in MNCs from adults
- induced by the heterodimer AHR/ARNT
Polymorphism
- Ala-189 allele may be a susceptibility factor for dioxin- related male infertility
- homozygosity for Ala-189 is observed in azoospermic individuals at higher frequency than in normozoospermic individuals
- Ala-189 might also be associated with susceptibility to & severity of endometriosis